Microwave assisted chemical synthesis instrument with controlled pressure release

ABSTRACT

An instrument for carrying out controlled microwave assisted chemical processes, and that is particularly useful for handling relatively small samples. The instrument includes a microwave-transparent reaction vessel with an open mouth, a pressure-resistant seal on the mouth of the vessel, and a needle, portions of which penetrate the seal with a first end of the needle and provide fluid communication into the vessel. A pressure transducer is at the opposite end of the needle and in fluid communication with the interior of the vessel through the needle. The instrument defines a pressure control flow path from a portion of the needle outside of the vessel to a fluid port, the flow path being in communication with the needle, the interior of the vessel and the transducer. A controllable pressure release valve for the flow path is associated with the port.

RELATED APPLICATIONS

This application is a divisional application of Ser. No. 10/126,838filed Apr. 19, 2002, now U.S. Pat. No. 7,282,184.

BACKGROUND

The present invention relates to the use of microwave assistedtechniques to carry out chemical reactions, particularly sophisticatedchemical synthesis reactions. More specifically, the invention relatesto an apparatus and method for controlled pressure release during suchsynthesis in a microwave-assisted instrument.

The present invention is related to copending and commonly-assignedapplication Ser. No. 09/773,846 filed Jan. 31, 2001, and now U.S. Pat.No. 6,753,517 by Jennings for Microwave-Assisted Chemical SynthesisInstrument With Fixed Tuning, the contents of which are incorporatedentirely herein by reference (“the '846 application”).

As set forth in the '846 application, interest has grown in the use ofmicrowave assisted techniques for chemical synthesis, particularlyorganic synthesis using relatively small amounts of reagents. The term“small” is used herein in a relative sense, but those familiar withmodern experimental synthesis techniques such as the development ofpharmaceuticals recognize that sample sizes of 5 milliliters (ml) orless are quite common, particularly when numerous sample reactions arebeing studied. In recent years, the availability and lowered cost ofcomputer processing power and memory has given rise in the areas ofchemical synthesis and analysis to automated and semi-automatedtechniques that carry out such chemical processes in relatively rapidfashion on large numbers of such small samples, and that quickly provideuseful information based on the completed processes. Thus, the potentialto include microwave assistance as a part of such processes offersanother method of increasing the speed with which they can be carriedout, and thus correspondingly increase the number of processes that canbe carried out within any given time frame.

The use of small amounts raises different problems than havetraditionally been raised in other areas of microwave-assisted chemistrysuch as digestion and loss-on-drying moisture content determinations.Such prior (and still extremely useful) microwave assisted techniquesand instruments have now been joined by this newer generation ofsophisticated microwave assisted instruments that can focus microwaveenergy on very small samples in a manner that heats the samples in adesired and controlled manner without overheating them or driving thereagents to decomposition. By way of comparison, complete ornear-complete decomposition is the goal of digestion, and thus excessive(relatively speaking) temperatures generally represent less of a processproblem. Chemical synthesis, however, has the goal of encouragingparticular reactants to act in an expected or predictable manner toproduce desired products. Thus, in many synthesis scenarios temperatureand pressure (among other factors) must be maintained within appropriatelimits.

In addition to the '846 application, other recent advances in microwaveassisted chemistry include (but are not limited to) those discussed inU.S. Pat. Nos. 6,320,170; 6,302,577; 6,268,570; 6,227,041; 5,796,080.

The '846 application discloses an instrument that can handle relativelysmall samples, typically liquid samples of organic materials, and thatcan apply precise and moderated amounts of microwave energy within itscavity to drive reactions carried out in vessels in the cavity in amanner appropriate to chemical synthesis. In particular, the '846application discloses a sophisticated structure for measuring thepressure inside of sealed vessels while reactions are proceeding. Asknown to those familiar with chemical synthesis, particularly in closedconditions, the pressure generated can be a measure of several factors,the primary ones typically being gaseous byproducts from the reaction,or an increase in gas temperature in accordance with the ideal gas laws,or both. Accordingly, pressure measurement is a valuable option in suchinstruments. In the '846 application, a reaction vessel, one version ofwhich resembles a classic test tube, is sealed in a pressure-resistantmanner with a metal cap and a flexible septum. A small needle ispositioned to pierce and penetrate the septum, and is in fluid (usuallygas) communication with a pressure transducer at the needle's oppositeend. Using the instrument, the pressure inside of the vessel can beconstantly monitored as a reaction proceeds and as microwave energy isapplied.

In the instrument described in the '846 application, however, the onlyway to release pressure inside the reaction vessel is to remove the capcompletely from the vessel (e.g. at the completion of a desiredreaction) or alternatively to remove the transducer from the needle. Inone case the reaction may be affected or interrupted, while in the otherthe ability to measure pressure is forfeited.

Furthermore, the instrument described in the '846 application lacks anyconvenient means for attaching the vessel to a gas source, should thatbe desired or required in particular circumstance.

Thus, although this is satisfactory in a number of circumstances, andalthough the instrument described in the '846 application is asignificant improvement in microwave-assisted synthesis techniques andinstrumentation, and has gained rapid commercial acceptance, the needstill exists for an apparatus in which pressure can be controllablyreleased (bled or vented) from a reaction vessel—or a gas addedthereto—as the reaction proceeds. Such potential release offers severaladvantages, such as the ability to keep pressure below a certainthreshold, or to drive a reaction towards completion by removing one ofthe reaction products from the environment in accordance withLeChatelier's principle. In this regard, gases are the products ofcertain reactions, and absent the capability to release or relieve theassociated increase in pressure in a closed environment, the reactionsmust be avoided in order to avoid pressure-related failure of thevessel.

In another aspect, lack of controlled communication with a closed vesselcan prevent the use of additional reagents, such as adding liquids orgases (as solvents or reagents) in order to carry out a later stage of amulti-step reaction.

Pressure-release vessels exist for microwave assisted chemistry, butgenerally in the context of preventing a pressure generated failure thatrenders the vessel unusable. For example, in commonly assigned U.S. Pat.Nos. 5,230,865 and 5,369,034 pressure release is provided by adisposable polymeric barrier (e.g. a rupture disk) positioned to blockone of the gas passageways between the pressurized interior of thereaction vessel and its lower-pressure (often atmospheric) surroundings.When the pressure inside the vessel exceeds the threshold of the barrier(which should be selected to be less than that of the remainder of thevessel), the barrier fails and the interior pressure is released.Although such pressure release is “controlled” in the sense that itprevents total failure of the vessel, it is uncontrolled in the sensethat the pressure cannot be monitored and adjusted as a reaction in thevessel proceeds.

The '034 and '865 patents also include a pressure bleed capability, butnot in conjunction with pressure measurement.

Commonly assigned U.S. Pat. No. 6,086,826 shows a different type ofpressure measurement in which a pressure transducer is mounted outsideof a closed vessel and the movement of the exterior of the vesselagainst the transducer gives a representative measurement of thepressure inside the vessel. This provides specific advantages when thepressure measurement device is best isolated from the reaction in thevessel, for example under particularly harsh chemical conditions such asdigestion. It does not, however, provide the more convenient temperaturemonitoring and control useful, and sometimes necessary, in synthesis ofsmall samples in more carefully controlled reactions.

Several patents to Floyd, including U.S. Pat. Nos. 4,904,450; 5,204,065and 5,264,185 also include a rupture-disk type of pressure reliefsystem. The Floyd '185 patent also includes a transducer, but therupture disk is positioned as a diaphragm between the vessel and thetransducer; i.e. there exist no direct fluid communication unless anduntil the rupture disks breaks under pressure. Thus pressure can only bemeasured in a secondary fashion, and provided the limits of the ruptureddisk are not exceeded.

Lautenschlager U.S. Pat. No. 5,725,835 discloses a device in which a gas(fluid) path extends from a reaction chamber to a series of valves, oneof which is electrically controlled, one of which is spring biased, oneof which is a simple rupture disk, and one of which operates manually.As set forth in FIG. 2 and the related discussion in the '835 patent,however, such pressure control is carried out between the reactionchamber and the valves rather than between individual vessels and thevalves.

Strauss U.S. Pat. No. 5,932,075 illustrates a vessel having a closure orcover that carries a number of control items, including a pressuremeasurement path, a separate pressure release path independent of thepressure measurement path, a sampling path, and a temperaturemeasurement device, the key feature of which, according to Strauss, isthe use of a heat exchanger (24 in several of the Strauss figures) thatpermits a reaction to be heated or cooled while in progress. The Straussdevice and its cover require a fair degree of complexity, however, andis potentially less conducive for repetitive use on larger numbers ofsmall samples.

Furthermore, other than the '846 application, none of these devicesprovides a practical structure or method for quickly carrying outnumerous reactions in sequential fashion. Stated differently, noneprovide a method or apparatus wherein reagents can be added to a numberof vessels following which the vessels can be sealed and placed in amicrowave cavity, can have the pressure and temperature therein measuredwhile microwaves are being applied, and can be removed from the cavity,all without opening the vessel or fatally breaching the seal.

Accordingly, the need exists for apparatus and related techniques thatcan carry out microwave-assisted synthesis on small samples while stillproviding the opportunity desired for controlled pressure release,including pressure release during ongoing reactions.

SUMMARY

Therefore, it is an object of the invention to providemicrowave-assisted synthesis on small samples combined with theopportunity for controlled pressure release, including pressure releaseduring ongoing reactions.

The invention meets this object with an instrument for carrying outcontrolled microwave assisted chemical processes, and that isparticularly useful for handling relatively small samples. In thisaspect, the instrument includes a microwave transparent reaction vesselwith an open mouth, a pressure resistant seal on the mouth of thevessel, a needle, portions of which penetrate the seal with a first endof the needed providing fluid communication into the vessel, a pressuretransducer at the opposite end of the needle and in fluid communicationwith the interior of the vessel through the needle, a pressurecontrolled flow path from a portion of the needle outside of the vesselto a fluid port, the flow path being in communication with the needle,the interior of the vessel and the transducer, and a controllablepressure release valve for the flow path and associated with the port.

In another aspect, the invention is an instrument for carrying outcontrolled microwave assisted chemical processes that includes amicrowave cavity, a vessel assembly that includes a microwavetransparent vessel, a seat in the cavity for receiving the vesselassembly and positioning at least portions of the vessel in themicrowave cavity, locking means for locking the vessel assembly in theseat, and a release mechanism for releasing the vessel assembly from theseat.

In another aspect, the invention is a method of carrying out microwaveassisted chemical reactions. In this aspect, the invention comprisesadding reagents to a microwave transparent vessel, securing the vesselagainst pressure release with a seal, thereafter inserting a needlethrough the seal and into the pressure-secured vessel to provide fluidcommunication to the interior of the sealed vessel through the needle,and radiating the vessel and its contents with microwaves.

In yet another aspect, the invention is an instrument that includes avessel assembly that includes a sealed vessel, a pressure moduleassembly that is removable and engageable with the vessel assembly andthat includes means, when engaged, for measuring the pressure inside ofthe sealed vessel, and an attenuator assembly for removeably receivingthe vessel assembly and the pressure assembly in engagement and forpositioning portions of the vessel in a microwave cavity and portions ofthe vessel and vessel assembly outside of the cavity while providing anattenuating barrier to the escape of microwaves from the cavity.

In yet another aspect, the invention is a pressure release structure fora microwave instrument that comprises a needle, a needle seal adjacentto the needle and having a shaft coaxial with the needle and incommunication therewith, a pressure transducer opposite the needle sealfrom the needle and in communication with the shaft, a housing holdingthe needle to the needle seal and the needle seal to the transducer, achamber formed between the housing and the needle seal, a lateral shaftthrough the needle seal from the coaxial shaft to the chamber in thehousing, and a valve in communication with the chamber.

In yet another aspect, the invention comprises a microwave attenuator, alock ring on the attenuator for locking the attenuator to a microwavecavity, an annular housing engageable with the lock ring, a plurality ofspring loaded pistons in the housing that are urged inwardly from theinner circumference of the housing toward the center, and means forcontrollably urging the pistons in a direction outwardly from the innercircumference of the housing.

The foregoing and other objects and advantages of the invention and themanner in which the same are accomplished will become clearer based onthe followed detailed description taken in conjunction with theaccompanying drawings in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a commercial embodiment of the presentinvention;

FIG. 2 is a partially disassembled perspective view of the pressuremodule assembly, the vessel assembly, and the attenuator assembly of thepresent invention;

FIG. 3 is a perspective view of a microwave cavity and associatedwaveguide as used in the present invention;

FIG. 4 is a cross sectional view of the attenuator assembly, vesselassembly, and pressure module assembly in their respective operatingpositions;

FIG. 4A is a cross sectional view of another embodiment of the pressurevessel assembly;

FIG. 5 is an exploded view of the pressure module assembly according tothe present invention;

FIG. 5A is an exploded view of the second embodiment of the pressuremodule assembly according to the present invention;

FIG. 6 is an enlarged cross sectional view of a portion of the firstembodiment of the pressure module assembly;

FIG. 7 is a partially exploded view of the attenuator assembly; and

FIG. 8 is a cross sectional view of the attenuator assembly of thepresent invention.

DETAILED DESCRIPTION

The present invention is an instrument for carrying out controlledmicrowave assisted chemical processes and that is particularly usefulfor handling relatively small samples. As set forth in the backgroundportion of the specification, the present invention is a continuingimprovement upon the instrument set forth in co-pending application Ser.No. 09/773,846. The '846 application is incorporated entirely herein byreference, and thus additional background to and advantages of theinvention are set forth in the '846 application.

FIG. 1 illustrates a commercial embodiment of the invention broadlydesignated at 10. Although the design set forth in FIG. 1 is exemplaryof a current commercial embodiment, it will be understood that thenature of the invention is such that FIG. 1's illustration is merelyillustrative of one version, and that the invention is not limited toits appearance in FIG. 1 or variations thereof. For illustrativepurposes, however, the position of the microwave cavity in theinstrument 10 is broadly designated at 11 in FIG. 1. The cavity itselfand its nature and operation are set forth in FIG. 3 herein, and infurther detail in the '846 application. FIG. 1 also illustrates that theinstrument preferably includes a housing formed of an upper portion 12and a lower portion 13. Because of the nature of the chemicalenvironment in which the instrument is typically used, the housingportions 12 and 13 are preferably formed of materials that are eitherresistant to most or many chemicals, or are coated with an appropriatecoating that is so resistant. Such materials are generally wellunderstood in this art and can be selected and implemented without undueexperimentation.

FIG. 2 illustrates three of the main components of the present inventionin partially-exploded fashion. These include the pressure-moduleassembly broadly designated at 14, the vessel assembly broadlydesignated at 15, and the attenuator assembly broadly designated at 16.Most of the details of the pressure-module assembly 14, the vesselassembly 15, and the attenuator assembly 16 will be set forth anddescribed in more detail with respect to other drawings herein.Nevertheless, FIG. 2 provides an appropriate overview of these parts andtheir general relationship to one another. Thus, FIG. 2 contains anumber of reference numerals which are described with respect to otherdrawings, rather than particularly with respect to FIG. 2. Thesereference numerals maintain their same meaning throughout thespecification and drawings. In general (and referring to furtherdescriptions herein), the vessel assembly 15 includes a sealed vessel(or “vial”) 25. The pressure module assembly 14 is removably engageablewith the vessel assembly 15 and includes means, when engaged, formeasuring the pressure inside of the sealed vessel 25. The attenuatorassembly 16 removably receives the vessel assembly 15 and the pressureassembly 14 in engagement and positions portions of the vessel 25 in amicrowave cavity and portions of the vessel 25 and vessel assembly 15outside of the cavity while providing an attenuating barrier to theescape of microwaves from the cavity. In particular, the relationshipbetween the vessel assembly 15 and the attenuator assembly 16 positionsthe needle 30 in the vessel 25 in a manner that avoids interferencebetween the needle 30 and microwave transmission in the cavity.

FIG. 3 illustrates a microwave cavity of the type described in the '846application and which is used in conjunction with the improvements ofthe present invention. In FIG. 3 the cavity is broadly designated at 17and is shown with a partially integrated waveguide portion 18 whichreceives microwaves initially from a microwave source (not shown) suchas a klystron, a magnetron, or potentially a solid state source such asa Gunn diode, and directs them to the cavity. In the preferredembodiments of the '846 application, the cavity 17 has a circular innercircumference 21 that includes a plurality of openings 22 through whichmicrowaves propagate from the waveguide 22 into the cavity 17. As alsoset forth in the '846 application, the cavity 17 includes a centralopening 23 in the floor 24 of the cavity. The opening 23 permits thevessel in the cavity 17 to be monitored, and preferably monitored fortemperature using a radiant monitoring device such as an infraredtemperature sensor. The remaining details of FIG. 3 are generallymechanical in nature and relate to the basic assembly of the parts usingrivets or screws or the like, and will not be discussed in detail hereinother than as necessary to describe the invention.

FIG. 4 illustrates a number of details and aspects of the invention. Theinvention includes a microwave transparent reaction vessel 25 with anopen mouth 26. A pressure resistant seal 27 (most clearly seen in FIG.2) is on the mouth 26 of the vessel 25. A needle 30 (which of course ishollow for fluid transmission purposes) has portions that penetrate theseal 27 with a first end of the needle 30 providing fluid (normally gas)communication into and with the vessel 25. The needle 30 is typically,although not necessarily, formed of metal.

A pressure transducer 31 is positioned at the opposite end of the needle30 and in fluid communication with the interior of the vessel 25 throughthe needle 30. Pressure transducers and their operation are wellunderstood in this art and a wide variety are commercially available.Thus, the transducer can be selected without undue experimentationprovided it fits into the housing and is calibrated to measure thepressures expected from the vessel 25.

The needle 30 is part of a pressure control flow path (that will also bedescribed in some detail with respect to FIG. 4 and other of thedrawings) from a portion of the needle 30 that is outside of the vessel25 to a fluid port 32 with the flow path being in communication with theneedle 30, the interior of the vessel 25, and the pressure transducer31. A controllable pressure release valve shown as the vent nut 33 ispart of the flow path and is associated with the port 32. The vent nut33 is probably the simplest example of a pressure release valve, and itwill be understood that more sophisticated devices can also beincorporated as desired or necessary.

The seal 27 on the vessel 15 preferably includes a penetrable septum 35(FIG. 2) for permitting the needle 30 to be inserted through the seal 27so that the vessel 15 can be sealed prior to inserting the needle 30.This offers particular advantages over the prior art in which the vesselseal typically carries an integral pressure release mechanism thatprevents a vessel from being filled and sealed in the absence of thepressure measuring device. The septum 35 is preferably formed of butylrubber or silicone, and has a thickness and composition sufficient toallow the needle to be inserted and removed while the septum 35re-closes and re-seals behind the needle 30 so that the vessel canremain sealed before the needle is inserted, while the needle isinserted, and after the needle has been removed. Although the number oftimes that a needle can be inserted and removed from a single septum isnot infinite, the ability to do it several times while maintaining apressure resistant seal offers significant advantages over seals andpressure measurement assemblies that require the vessel to be opened inorder to change or remove the pressure measuring device.

As perhaps best illustrated in FIG. 2, the seal 27 preferably forms acap that includes a metal portion 34 and the septum 35 in concentricrelationship to one another. The metal portion 34 of the seal 27provides for an excellent clamping seal between the seal 27 and thevessel 15 while still permitting the incorporation of the penetrableseptum 35.

As in other microwave applications, the microwave transparent materialselected for the vessel 15 can be any material that is appropriatelytransparent to microwave frequencies and which can withstand, based uponits composition, design and structure, the pressures expected to occurin any given reaction. Commonly preferred materials for vessels includeglass, quartz, various polymers including engineering polymers, and insome cases combinations of these materials. In many circumstances, thevessel 15 will resemble a glass test tube or glass laboratory flask,which offer certain advantages, but the invention and its use andadvantages are not so limited.

Accordingly, the instrument of the present invention provides theprocess advantage of adding reagents to a reaction vessel, then sealingthe vessel and placing it in a microwave cavity, then measuring itstemperature and pressure without opening the vessel or fatally breachingits seal, and then removing the vessel from the cavity and from thepressure measuring instrument, all while maintaining the seal intact.Such capability adds the further capability of pre-filling a number ofvessels with the desired reagents (or with reagents that differ,slightly or greatly, from vessel to vessel) and then sequentiallycarrying out microwave assisted chemistry techniques on the contents ofthe vessel, and again without opening the vessels. The sequential andrelatively rapid treatment of a plurality of vessels also has obviousbenefits for automated processes, such as those often referred to as“combinatorial” techniques.

The manner in which the invention allows for controlled pressure releaseis best illustrated by taking the views of FIGS. 4, 5 and 6 incombination. Each of these figures shows that in preferred embodiments aneedle seal 36 is positioned between the needle 30 and the pressuretransducer 31. These elements are in turn assembled and held together ina housing 37. The needle seal 36 has an internal shaft 40, most clearlyillustrated in FIG. 6, that is coaxial with the needle 30 and incommunication with the needle 30 to thereby provide direct fluid (gas)communication from the interior of the vessel 15 through to the pressuretransducer 31. FIG. 6 also shows that the housing 37 holds the needle 30to the needle seal 36, and the needle seal 36 to the transducer 31. Inparticular, FIGS. 4, 5 and 6 illustrate that both the needle seal 36 andthe housing 37 are cylindrical, and that the housing 37 surrounds theneedle seal 36. The needle seal 36 has an outer diameter that isslightly less than the inner diameter of the housing 37. As a result,the housing 37 and the needle seal 36 form an annular chamber 41therebetween.

The needle seal 36 also includes a lateral shaft 42 (i.e., one that isnot coaxial with the needle 30) through the needle seal 36 from thecoaxial shaft 40 to the annular chamber 41.

Returning to FIG. 4, it will be seen that the annular chamber 41 is incommunication with the port 32 through the port shaft 43, which inpreferred embodiments is threaded into the port opening 44. FIG. 4 showsthe lateral shaft 42 as the small circle normal to the drawing in themiddle of the coaxial shaft 40 in the needle seal 36. The vent nut 33serves as a preferred valve embodiment for the port 32. FIGS. 4, 5 and 6thus illustrate the manner in which pressure can be controllablyreleased from the sealed vessel 15 at any time, including during theapplication of microwave frequencies to the contents of the vessel 15;i.e. as a desired chemical reaction is proceeding. FIGS. 4, 5 and 6illustrate the lateral shaft 42 as being perpendicular to the coaxialshaft 40, but it will be understood that this is a preferred embodiment,and that the communication between and among the coaxial shaft 40, thelateral shaft 42 and the annular chamber 41 could be made at differentangles or orientations while functioning in entirely the same manner asthe illustrated embodiment. Indeed, given the nature and behavior offluids (particularly gases) even alternative or more contorted pathwayscould serve this purpose.

FIGS. 4 and 5 illustrate additional mechanical details of the preferredembodiment illustrated therein. The needle 30 is incorporated into thehousing 37 using a needle screw 45. A retaining flange 46 and a seal cap47 are part of the pressure-module assembly 14, and help keep thepressure-module assembly 14 engaged with the attenuator assembly 16 in amanner to be described with respect to FIGS. 7 and 8. A cap spring 50helps urge the parts into proper relationship when assembled, as bestseen in FIG. 4.

FIG. 5 also illustrates that the needle seal 36 includes a pair ofO-rings 51, which help orient it properly within the housing 37 toproperly define the annular chamber 41.

The retaining flange 36 helps hold the seal cap in place when no vesselis in position, and the spring 50 helps urge the seal cap 47 downwardlyin an appropriate orientation.

FIG. 5 also illustrates the switch 52 and its spacer 53. The spacer 53only touches the switch when the spacer 53 touches the vessel 15, thusgiving the switch 52 a contact or no-contact signal during operation ofthe instrument.

FIG. 4 also illustrates a transducer wire 48 for providing a signalcommunication path between the transducer and the appropriateprocessors. In all other aspects, the embodiment of FIG. 4A operates thesame as the embodiment illustrated in FIG. 4.

FIG. 4A illustrates a second embodiment of the pressure module assembly14 according to the present invention. FIG. 4A includes a number ofelements that are common to FIGS. 4, 5 and 6, and illustrates that in analternative embodiment, the needle seal 36 can be formed of a largersingle portion rather than as an insert in the housing 37. This reducesthe size of the housing 37 and eliminates two of the three O-rings 51that are illustrated in FIG. 4. In this embodiment, the port shaft 43extends entirely through the needle seal 36 from the exterior of thepressure module assembly 14 to the coaxial shaft 40.

In the same fashion, FIG. 5A illustrates the embodiment of FIG. 4A inexploded fashion. Given that all of the relevant parts have already beendiscussed, the operation of the embodiment of FIG. 5A will be understoodin accordance with the previous descriptions herein.

It will be understood that electrical connection to the transducer 31 ismade through the cable or wire 48 (FIGS. 4A and 5A) that enters thehousing 37 through the strain relief 54 and the flange 55. A pair ofscrews 56 are used to assemble the flange 55 to the housing 37.

Aspects of the attenuator assembly 16 are also illustrated in FIG. 4,but are more easily understood using the orientation of FIGS. 7 and 8which show the attenuator assembly in more detail. As familiar to thoseof ordinary skill in these arts, microwaves have a frequency range thatis typically described as being between about 300 megahertz and 300gigahertz, which corresponds to wavelengths of between about 1millimeter and 1 meter. Electromagnetic radiation of these frequenciesand wavelengths can interfere with other devices, or can even havepotentially harmful medical effects such as interference with cardiacpacemakers, or can produce other undesired results. Accordingly, forthese and other reasons, microwave instruments generally should includesome form of attenuator; i.e., a means of limiting the application ofmicrowaves to the desired reaction materials and vessels. In manycircumstances, this is done by applying the microwaves entirely inside aclosed cavity of the type that can be opened and closed in a manner assimple as a door. When made of metal (including metal screening of anappropriate size), the cavity serves as an effective barrier tomicrowave transmission.

For other types of reactions, however, open reaction systems, in whichthe cavity is open to some extent to the ambient surroundings, are moreconvenient. In such cases, an attenuator is used to prevent the unwantedtransmission of microwaves to the ambient surroundings. An attenuator isgenerally formed of a structure, often cylindrical, that provides anopening into the cavity which is sufficient for the desired vessels, butwhich has a length and diameter, which prevents certain wavelengths fromescaping. The use and sizing of such attenuators is well understood inthe art and need not be discussed herein in detail other than to notethat an attenuator in the form of a cylinder should have a diametersmaller than the propagated wavelength (λ) and a length that is at leastone-fourth of the propagated wavelength.

Furthermore, because the advantages set forth in the co-pending andincorporated '846 application, include the advantage of being able toquickly and easily change reaction vessels into and out of the cavity,the present invention includes an appropriate attenuator assembly forpreventing the escape of microwaves in such circumstances.

Thus, FIG. 7 shows a number of details of the attenuator assembly 16.The attenuator assembly 16 first includes the attenuator itselfdesignated at 57. A lock ring 60 attaches to the attenuator 57 andincludes a locking flange 61 for locking the attenuator into a microwavecavity that has an appropriate corresponding locking channel. A housing62 holds the lock ring and the attenuator to one another and because thepreferred attenuator is cylindrical in shape (but not necessarily so)the lock ring is 60 and the housing 62 are similarly annular in theirgeometry.

In addition to providing an attenuator against the undesiredtransmission of microwaves outside of the instrument, the attenuatorassembly 16 provides a seat for receiving the pressure module assembly14 for seating the vessel 15 in the cavity and positioning at leastportions of the vessel 15 in the cavity. The lock ring 60 and lockingflange 61 provide means for locking the attenuator in the cavity, andthe attenuator itself further includes locking means described hereinfor locking the vessel assembly 15 and the pressure module assembly 14in the seat formed by the cavity and the attenuator. Furthermore, inorder to provide for rapid and convenient engagement and disengagementof the vessel and pressure assembly from the cavity, the attenuatorassembly 16 includes a release mechanism for releasing the pressuremodule assembly and vessel assembly respectively from their seatedposition in the cavity.

Turning to the release mechanism in more detail, in the preferred andillustrated embodiment it includes a plurality of spring-loaded pistons63 in the attenuator housing 62. The pistons 63 are positioned inrespective cylinders 64 in the attenuator housing 62. The pistons 63 areurged circumferentially inwardly in the attenuator housing 62 by thecombination of the springs 65 and the cover plates 66 which in turn areheld to the attenuator housing 62 by the screws 67. In this manner, andabsent any opposing force, the pistons 63 extend inwardly into thecircular opening formed by the attenuator 57 and the attenuator housing62. Each of the pistons 63 include a chamfered edge 70, however, so thatwhen the pressure module assembly 14 is inserted into the attenuatorassembly 16, the pistons retreat slightly under this engagement, andthen re-engage the pressure module assembly by clamping over a ledge orshoulder 71 formed around the housing 37 of the pressure module assembly14. In this manner, the pressure module assembly can be easily insertedand locked into place in the attenuator assembly 16 with the lowerportions of the pistons 63 engaging the top portions of the shoulder 71.

In order to make sure that the pistons 63 are always oriented with thechamfered edge 70 facing up, each piston 63 also includes a small shaft72 that in conjunction with an appropriate opening (FIG. 4) clocks thepiston 63 in the proper orientation. An O-ring 73 also helps to seat thepiston properly in the cylinder 64 while still providing for the biasedmovement urged by the springs 65.

In order to remove the pressure module assembly 14 from the attenuatorassembly 16, the invention includes means for controllably urging thepistons 63 in a direction outwardly from the inner circumference of theattenuator housing 62. In FIG. 7, a first part of this mechanism isillustrated as the channel 74 in the attenuator 57.

The channel 74 works in conjunction with a port 75 for compressed airbest illustrated in FIG. 2. When the attenuator assembly 16 isassembled, the compressed air port 75 is in fluid communication with thechannel 74. Thus, when compressed air is fed into the compressed airport 75, it travels through the channel 74 and urges the pistons 63outwardly against the bias of the springs 65. By so urging the pistons63 backwardly, the use of the compressed air releases the pressuremodule assembly 14 from the attenuator assembly 16. Although compressedair is a convenient fluid to use in this manner (i.e., inert,inexpensive and generally convenient), it will be understood that therelease mechanism is not limited to compressed air, and that othergases, and potentially some liquids, could serve this purpose.

As FIG. 7 illustrates, in preferred embodiments the pistons 63 arespaced equidistantly from one another around the circumference of theattenuator housing 62. FIG. 7 illustrates an embodiment with threepistons 63 set at angles of 120 degrees to one another. It will beunderstood, of course, that a single piston can serve as a lockingdevice and that four or more pistons could be incorporated, all withinthe scope of the invention.

FIG. 7 also illustrates that the attenuator assembly can be assembledusing the set screws 76, although again the use of set screws is oneembodiment, rather than a limitation of the invention. Similarly, inother circumstances the number of individual parts illustrated in FIG. 7could be reduced as desired by those of skill in the art all whileoperating within the scope of the invention.

FIG. 8 is a cross-sectional view of the unexploded attenuator assembly16. FIG. 8 illustrates a number of the same features as set forth inFIG. 7, but in a different orientation that helps with an understandingof the operation of the illustrated embodiment. The air inlet port isagain designated at 75 and the resulting channel 74 is in communicationtherewith. FIG. 8 also shows the pistons 63 in an engaged position, aswell as a central opening 77 in the attenuator, portions of which arealso illustrated in FIGS. 2 and 7. FIG. 8 illustrates portions of theattenuator 57 and the housing 62, as well as the lock flanges 61 thatare a portion of the lock ring 60. As described with respect to theprevious figures, the pistons 63 are urged circumferentially inwardly bythe springs 65 which are held in place by the cover plates 66 and thescrews 67.

Although the instrument has been described herein in terms of thehelpful communication between and among the needle, the transducer andthe pressure release valve, it will be understood that these elementscan be favorably used independently from one another. For example, byincorporating a flexible septum that moves in response to the pressureinside the vessel, the transducer can be positioned in pressurecommunication with the septum, rather than the needle. This isparticularly useful when the instrument is used to handle materials thatwould be corrosive to the transducer. In such cases the needle can beeliminated (if pressures are expected to remain low enough) or the flowpath between the vessel and its surroundings can be isolated from thetransducer.

In the same manner, where pressure release (or other fluidcommunication) is desired but specific pressure measurement is optionalor unnecessary, the transducer can be eliminated entirely, while theinstrument still takes advantage of the pressure release feature.

In another aspect, the invention is a method of carrying out microwaveassisted chemical reactions. In this aspect, the method comprises addingreagents to a microwave transparent vessel, securing the vessel againstpressure release with a seal, inserting a needle through a seal and intothe pressure secured vessel to provide a fluid communication to theinterior of the sealed vessel through the needle, communicating with afluid between the interior of the sealed vessel and its ambientsurroundings without otherwise breaching the seal and then irradiatingthe vessel and its contents with microwaves.

As used herein, the term “communicating with a fluid” refers to thepassage of gases or liquids between the vessel and it surroundings, andcan include pressure release from the vessel to the surroundings, or theaddition of gases or liquids to the vessel from its surroundings, allwithout fatally or finally breaching the seal.

As described herein with respect to the instrument aspects of theinvention, because the septum is resealable, the method can furthercomprise, removing the needle from the vessel following the step ofirradiating the vessel and then inserting the needle into a seconddifferent vessel following the step of removing it from the initialvessel, or in a complimentary fashion, re-inserting the needle into theoriginal vessel. In such cases, the method can further compriseirradiating the second vessel, or the vessel with the needle reinsertedwith microwaves following the step of inserting the needle.

In accordance with the device set forth in the incorporated '846application, the method can further comprise monitoring the temperatureof the vessel or its contents while irradiating the vessel and itscontents with microwaves. Similarly, the invention provides theinstrumentation for the method step of monitoring the pressure of thevessel; i.e. of its contents; while eradiating the vessel and itscontent with microwaves.

The method can further comprise moderating the application of microwavesto the vessel and its contents based on the monitored results of eitherthe pressure or the temperature. The pressure monitoring can, of course,be accomplished using the instrument described herein. The temperaturemonitoring can be carried out in a suitable manner using infrareddetection in a manner described in the incorporated '846 application.Infrared monitoring of the temperature of a sample being irradiated withmicrowaves is also described in commonly assigned U.S. Pat. No.6,277,041. The monitored information can be forwarded to an appropriateprocessor, which in turn can control the application of microwaves usingone or more of several moderating techniques. One moderating techniqueincludes the use of a switching power supply as set forth in commonlyassigned U.S. Pat. Nos. 6,084,226 and 6,288,379. Another method ofmoderating the application of microwaves in response to a monitoredtemperature or pressure is set forth in commonly assigned U.S. Pat. No.5,796,080.

Furthermore, in a related aspect the invention is a method of carryingout microwave-assisted chemical reactions on a plurality of reagent andvessel combinations. In this aspect the method comprises adding reagentsto a plurality of microwave-transparent vessels and securing each of thevessels against pressure release with a seal. Thereafter, the methodincludes inserting a needle through the seal of a first of the vesselsand into the pressure-secured vessel to provide fluid communication tothe interior of the sealed vessel through the needle, then irradiatingthe vessel and its contents with microwaves while monitoring thepressure inside and temperature of the vessel, then moderating theapplication of microwaves to the vessel in response to the monitoredtemperature and pressure and then removing the needle from the firstvessel following the irradiation and moderating steps and withoutpermanently or fatally breaching the seal of the vessel. In particular,this aspect of the method includes the step or steps of repeating theinserting, irradiating, monitoring, moderating and removing steps forthe second and successive vessels of the plurality of vessels.

In particular circumstances, the method comprises adding a different setof reagents to at least the second vessel, or adding a different set ofreagents to each vessel. In turn, the step of moderating the applicationof microwaves can include moderating the microwave power, moderating theduty cycle, or physically moderating the transmission of microwavesbetween a microwave source and the vessel.

In this aspect the step of monitoring the temperature can compriseoptically monitoring the temperature without invading the vessel, andthe step of monitoring the pressure can comprise monitoring the pressurewith a transducer positioned in the sealed flow path that communicateswith the interior of the vessel through the needle, as described hereinwith respect to the structural aspects of the invention.

In the drawings and specification there has been set forth preferredembodiments of the invention, and although specific terms have beenemployed, they are used in a generic and descriptive sense only and notfor purposes of limitation, the scope of the invention being defined inthe claims.

1. An instrument for carrying out controlled microwave assisted chemicalprocesses, and that is particularly useful for handling relatively smallsamples, said instrument comprising: a microwave cavity; a vesselassembly including a microwave transparent vessel; a seat in said cavityfor receiving said vessel assembly and positioning at least portions ofsaid vessel in said microwave cavity; a plurality of pistons in saidseat that are urged circumferentially inwardly against said assemblywhen said assembly is seated for locking said vessel assembly in saidseat; a valve in fluid communication with said vessel; and a releasemechanism for releasing said vessel assembly from said seat.
 2. Aninstrument according to claim 1 wherein said vessel assembly comprises ashoulder, upper portions of which engage lower portions of said pistonswhen said vessel assembly is seated in said cavity.
 3. An instrumentaccording to claim 1 wherein said seat further comprises means forreleasing said pistons from said set holes for thereby releasing saidvessel assembly from said seat.
 4. An instrument according to claim 3wherein said release means comprises: a channel between said vesselassembly and said seat that communicates with said pistons; and meansfor sending compressed air thorough said channel to thereby urge saidpistons circumferentially outwards and release said vessel assembly fromits seated position in said cavity.
 5. An instrument for carrying outcontrolled microwave assisted chemical processes, and that isparticularly useful for handling relatively small samples, saidinstrument comprising: a vessel assembly that includes a sealed,microwave transparent vessel and a pressure resistant,mechanically-penetrable seal on the mouth of said vessel, wherein saidseal includes a penetrable septum; a valve in fluid communication withsaid vessel; a pressure module assembly that is removably engageablewith said vessel assembly and that includes means, when engaged, formeasuring the pressure inside of said sealed vessel; and an attenuatorassembly for removably receiving said vessel assembly and said pressureassembly in engagement and for positioning portions of said vessel in amicrowave cavity and portions of said vessel and vessel assembly outsideof said cavity while providing an attenuating barrier to the escape ofmicrowaves from said cavity.
 6. An instrument according to claim 5 andfurther comprising a microwave cavity with said attenuator assemblyengaged therewith.
 7. An instrument according to claim 6 and furthercomprising a microwave source in communication with said cavity fordirecting microwave radiation into said cavity.
 8. An instrumentaccording to claim 5 wherein said pressure module assembly includes aneedle for penetrating said septum and a pressure transducer in sealedcommunication with said needle for measuring the pressure inside of saidvessel as a reaction is proceeding.
 9. An instrument according to claim8 wherein said pressure module assembly further comprises a controllablevent port in communication with said needle at a position between saidvessel and said transducer.
 10. An instrument according to claim 8wherein the relationship between said vessel assembly and saidattenuator assembly positions said needle in said vessel in a mannerthat avoids interference between said needle and microwave transmissionin said cavity.